This study investigates the combined effects of pyrogallol (PG) and microplastics (MPs) on the freshwater crayfish Procambarus clarkii, evaluating their impacts both individually and in combination. Over 15 days, crayfish were exposed to 100 mg/L MPs, 10 mg/L PG, and a mixture of 10 mg/L PG + 100 mg/L MPs. The activities of serum lysozyme (LYZ), phenoxide (Phx), and acid phosphatase (ACP), along with neurological markers such as acetylcholinesterase (AchE) and nitric oxide (NO), were measured. Histological alterations in the intestines were also assessed. Results indicated that both PG and MPs, separately or jointly, decreased immune parameters (LYZ, Phx, ACP) and neurotoxic indicators (AchE, NO). Histologically, crayfish exposed to PG and MPs showed significant intestinal damage, including epithelial disorganization, tissue tearing, and necrosis, with combined exposure exacerbating these effects. These findings suggest that PG and MPs interact synergistically, particularly regarding histopathological changes, highlighting the need for monitoring wastewater effluents in aquatic ecosystems.